7BXU

CLC-7/Ostm1 membrane protein complex

7BXU の概要

• エントリーDOI: 10.2210/pdb7bxu/pdb
• EMDBエントリー: 30238
• 分子名称: Osteopetrosis-associated transmembrane protein 1, H(+)/Cl(-) exchange transporter 7, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: complex, lysosome, transporter, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 255225.80

構造登録者

Zhang, S.S.,Yang, M.J. (登録日: 2020-04-20, 公開日: 2020-09-16, 最終更新日: 2024-10-16)

主引用文献

Zhang, S.,Liu, Y.,Zhang, B.,Zhou, J.,Li, T.,Liu, Z.,Li, Y.,Yang, M.
Molecular insights into the human CLC-7/Ostm1 transporter.
Sci Adv, 6:eabb4747-eabb4747, 2020

PubMed Abstract: CLC family proteins translocate chloride ions across cell membranes to maintain the membrane potential, regulate the transepithelial Cl transport, and control the intravesicular pH among different organelles. CLC-7/Ostm1 is an electrogenic Cl/H antiporter that mainly resides in lysosomes and osteoclast ruffled membranes. Mutations in human CLC-7/Ostm1 lead to lysosomal storage disorders and severe osteopetrosis. Here, we present the cryo-electron microscopy (cryo-EM) structure of the human CLC-7/Ostm1 complex and reveal that the highly glycosylated Ostm1 functions like a lid positioned above CLC-7 and interacts extensively with CLC-7 within the membrane. Our complex structure reveals a functionally crucial domain interface between the amino terminus, TMD, and CBS domains of CLC-7. Structural analyses and electrophysiology studies suggest that the domain interaction interfaces affect the slow gating kinetics of CLC-7/Ostm1. Thus, our study deepens understanding of CLC-7/Ostm1 transporter and provides insights into the molecular basis of the disease-related mutations.

PubMed: 32851177
DOI: 10.1126/sciadv.abb4747

実験手法

ELECTRON MICROSCOPY (3.7 Å)